A Multicenter, Double-Blind, Randomized, Comparative Study To Evaluate The Safety, Tolerability, And Efficacy Of MK-0991 Versus (Amphotericin B) Liposome For Injection As Empirical Therapy In Patients With Persistent Fever And Neutropenia
16 Years
N/A
Both
Cancer
Trial Information
A Multicenter, Double-Blind, Randomized, Comparative Study To Evaluate The Safety, Tolerability, And Efficacy Of MK-0991 Versus (Amphotericin B) Liposome For Injection As Empirical Therapy In Patients With Persistent Fever And Neutropenia
OBJECTIVES:
- Compare the number of successful treatment outcomes among patients treated with
caspofungin acetate vs amphotericin B liposomal for persistent fever and neutropenia
following cancer therapy, in terms of survival for 7 days after study drug, resolution
of fever, treatment of any baseline fungal infection, absence of breakthrough fungal
infection during and for 7 days after study drug, and absence of study drug
discontinuation due to toxicity or lack of efficacy.
- Compare the incidence of nephrotoxicity in patients treated with these regimens.
- Compare the incidence of infusion-related adverse events within 1 hour of the infusion
in patients treated with these regimens.
- Compare the incidence of treatment discontinuation due to drug-related adverse events,
frequency of drug-related events, number of breakthrough fungal infections, and number
of successfully treated baseline fungal infections in patients treated with these
regimens.
- Compare incidence of required dose increase due to inadequate clinical response in
patients treated with these regimens.
- Compare the time to resolution of fever in patients treated with these regimens.
OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients
are stratified according to high-risk (prior allogeneic bone marrow transplantation or prior
chemotherapy for relapse of acute leukemia) vs low-risk and prior prophylactic antifungal
therapy during chemotherapy (yes vs no). Patients are randomized to one of two treatment
arms.
- Arm I: Patients receive caspofungin acetate IV over 1 hour followed by placebo IV over
2 hours.
- Arm II: Patients receive placebo IV over 1 hour followed by amphotericin B liposomal IV
over 2 hours.
Treatment repeats daily for up to 28 days in the absence of disease progression or
unacceptable toxicity.
Patients are followed at 7 and 14 days after study drug discontinuation.
PROJECTED ACCRUAL: A total of 1060 patients (530 per arm) will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Leukemia, lymphoma, or other cancer that has been previously treated with
chemotherapy or bone marrow or peripheral blood stem cell transplantation
- Absolute neutrophil count less than 500/mm^3 for past 96 hours and not expected to
recover in next 48 hours
- Received at least 96 hours of parenteral systemic antibacterial therapy
- Fever greater than 38.0 degrees Celsius
- Adequately managed bacterial infection allowed if all of the following are true:
- Negative blood cultures
- Received at least 5 days of antibiotics to which any bacterial isolates are
sensitive
- Surgical drainage of any abscess fluid or surgical debridement of infected
tissues
- Removal of infected catheters
- No invasive fungal infection
- Not previously enrolled on this study
PATIENT CHARACTERISTICS:
Age:
- 16 and over
Performance status:
- Karnofsky 30-100%
Life expectancy:
- At least 5 days
Hematopoietic:
- Platelet count at least 5,000/mm^3
- INR no greater than 1.6 (no greater than 4.0 if receiving anticoagulants)
Hepatic:
- Bilirubin no greater than 3 times upper limit of normal (ULN)
- AST or ALT no greater than 5 times ULN
- Alkaline phosphatase no greater than 3 times ULN
- No acute hepatitis or cirrhosis
Renal:
- Not specified
Other:
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective barrier contraception
- No allergy, hypersensitivity, or prior serious reaction to any echinocandin
antifungal or amphotericin B formulation
- No other condition or illness that would preclude study participation
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- See Disease Characteristics
Chemotherapy:
- See Disease Characteristics
- No concurrent investigational antineoplastic therapy
Endocrine therapy:
- Not specified
Radiotherapy:
- Not specified
Surgery:
- Not specified
Other:
- At least 10 days since prior parenteral amphotericin B
- At least 14 days since prior investigational antibiotic, antifungal, or
immunosuppressive drug
- No concurrent rifampin or cyclosporine
- No other concurrent investigational antibiotic, antifungal, or immunosuppressive drug
- No concurrent alcohol
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Masking: Double-Blind, Primary Purpose: Supportive Care
Principal Investigator
Kent Sepkowitz, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Memorial Sloan-Kettering Cancer Center
Authority:
United States: Federal Government
Study ID:
00-085
NCT ID:
NCT00008359
Start Date:
August 2000
Completion Date:
Related Keywords:
- Cancer
- stage I adult Hodgkin lymphoma
- stage II adult Hodgkin lymphoma
- stage III adult Hodgkin lymphoma
- stage IV adult Hodgkin lymphoma
- stage IV breast cancer
- stage IIIA breast cancer
- monoclonal gammopathy of undetermined significance
- stage IIIB breast cancer
- recurrent adult Hodgkin lymphoma
- stage I cutaneous T-cell non-Hodgkin lymphoma
- stage II cutaneous T-cell non-Hodgkin lymphoma
- stage III cutaneous T-cell non-Hodgkin lymphoma
- stage IV cutaneous T-cell non-Hodgkin lymphoma
- recurrent cutaneous T-cell non-Hodgkin lymphoma
- isolated plasmacytoma of bone
- extramedullary plasmacytoma
- refractory multiple myeloma
- stage II ovarian epithelial cancer
- stage III ovarian epithelial cancer
- stage IV ovarian epithelial cancer
- recurrent ovarian epithelial cancer
- disseminated neuroblastoma
- recurrent neuroblastoma
- recurrent Wilms tumor and other childhood kidney tumors
- stage 0 chronic lymphocytic leukemia
- Waldenstrom macroglobulinemia
- stage I multiple myeloma
- stage II multiple myeloma
- stage III multiple myeloma
- stage I chronic lymphocytic leukemia
- stage II chronic lymphocytic leukemia
- stage III chronic lymphocytic leukemia
- stage IV chronic lymphocytic leukemia
- recurrent adult acute myeloid leukemia
- recurrent adult acute lymphoblastic leukemia
- relapsing chronic myelogenous leukemia
- refractory chronic lymphocytic leukemia
- small intestine lymphoma
- stage III malignant testicular germ cell tumor
- recurrent malignant testicular germ cell tumor
- unspecified adult solid tumor, protocol specific
- chronic phase chronic myelogenous leukemia
- accelerated phase chronic myelogenous leukemia
- blastic phase chronic myelogenous leukemia
- meningeal chronic myelogenous leukemia
- adult acute myeloid leukemia in remission
- adult acute lymphoblastic leukemia in remission
- polycythemia vera
- primary myelofibrosis
- essential thrombocythemia
- fever, sweats, and hot flashes
- testicular embryonal carcinoma
- testicular choriocarcinoma
- testicular teratoma
- testicular yolk sac tumor
- testicular embryonal carcinoma and teratoma
- testicular embryonal carcinoma and teratoma with seminoma
- testicular embryonal carcinoma and yolk sac tumor
- testicular embryonal carcinoma and yolk sac tumor with seminoma
- testicular embryonal carcinoma and seminoma
- testicular yolk sac tumor and teratoma
- testicular yolk sac tumor and teratoma with seminoma
- testicular choriocarcinoma and yolk sac tumor
- testicular choriocarcinoma and embryonal carcinoma
- testicular choriocarcinoma and teratoma
- testicular choriocarcinoma and seminoma
- progressive hairy cell leukemia, initial treatment
- refractory hairy cell leukemia
- stage I grade 1 follicular lymphoma
- stage I grade 2 follicular lymphoma
- stage I grade 3 follicular lymphoma
- stage I adult diffuse small cleaved cell lymphoma
- stage I adult diffuse mixed cell lymphoma
- stage I adult diffuse large cell lymphoma
- stage I adult immunoblastic large cell lymphoma
- stage I adult lymphoblastic lymphoma
- stage I adult Burkitt lymphoma
- recurrent ovarian germ cell tumor
- chronic myelomonocytic leukemia
- T-cell large granular lymphocyte leukemia
- ovarian yolk sac tumor
- ovarian embryonal carcinoma
- ovarian polyembryoma
- ovarian choriocarcinoma
- ovarian immature teratoma
- ovarian mature teratoma
- ovarian monodermal and highly specialized teratoma
- ovarian mixed germ cell tumor
- acute undifferentiated leukemia
- stage III grade 1 follicular lymphoma
- stage III grade 2 follicular lymphoma
- stage III grade 3 follicular lymphoma
- stage III adult diffuse small cleaved cell lymphoma
- stage III adult diffuse mixed cell lymphoma
- stage III adult diffuse large cell lymphoma
- stage III adult immunoblastic large cell lymphoma
- stage III adult lymphoblastic lymphoma
- stage III adult Burkitt lymphoma
- stage IV grade 1 follicular lymphoma
- stage IV grade 2 follicular lymphoma
- stage IV grade 3 follicular lymphoma
- stage IV adult diffuse small cleaved cell lymphoma
- stage IV adult diffuse mixed cell lymphoma
- stage IV adult diffuse large cell lymphoma
- stage IV adult immunoblastic large cell lymphoma
- stage IV adult lymphoblastic lymphoma
- stage IV adult Burkitt lymphoma
- recurrent grade 1 follicular lymphoma
- recurrent grade 2 follicular lymphoma
- recurrent grade 3 follicular lymphoma
- recurrent adult diffuse small cleaved cell lymphoma
- recurrent adult diffuse mixed cell lymphoma
- recurrent adult diffuse large cell lymphoma
- recurrent adult immunoblastic large cell lymphoma
- recurrent adult lymphoblastic lymphoma
- recurrent adult Burkitt lymphoma
- stage I adult T-cell leukemia/lymphoma
- stage II adult T-cell leukemia/lymphoma
- stage III adult T-cell leukemia/lymphoma
- stage IV adult T-cell leukemia/lymphoma
- recurrent adult T-cell leukemia/lymphoma
- secondary acute myeloid leukemia
- de novo myelodysplastic syndromes
- high risk metastatic gestational trophoblastic tumor
- previously treated myelodysplastic syndromes
- secondary myelodysplastic syndromes
- primary central nervous system non-Hodgkin lymphoma
- neutropenia
- infection
- prolymphocytic leukemia
- AIDS-related peripheral/systemic lymphoma
- AIDS-related primary CNS lymphoma
- primary systemic amyloidosis
- intraocular lymphoma
- stage I mantle cell lymphoma
- contiguous stage II grade 1 follicular lymphoma
- contiguous stage II grade 2 follicular lymphoma
- contiguous stage II grade 3 follicular lymphoma
- contiguous stage II adult diffuse small cleaved cell lymphoma
- contiguous stage II mantle cell lymphoma
- contiguous stage II adult diffuse mixed cell lymphoma
- contiguous stage II adult immunoblastic large cell lymphoma
- contiguous stage II adult diffuse large cell lymphoma
- contiguous stage II adult Burkitt lymphoma
- contiguous stage II adult lymphoblastic lymphoma
- noncontiguous stage II grade 1 follicular lymphoma
- noncontiguous stage II grade 2 follicular lymphoma
- noncontiguous stage II grade 3 follicular lymphoma
- noncontiguous stage II adult diffuse small cleaved cell lymphoma
- noncontiguous stage II mantle cell lymphoma
- noncontiguous stage II adult diffuse mixed cell lymphoma
- noncontiguous stage II adult immunoblastic large cell lymphoma
- noncontiguous stage II adult diffuse large cell lymphoma
- noncontiguous stage II adult Burkitt lymphoma
- noncontiguous stage II adult lymphoblastic lymphoma
- stage III mantle cell lymphoma
- stage IV mantle cell lymphoma
- recurrent mantle cell lymphoma
- angioimmunoblastic T-cell lymphoma
- anaplastic large cell lymphoma
- stage I mycosis fungoides/Sezary syndrome
- stage II mycosis fungoides/Sezary syndrome
- stage III mycosis fungoides/Sezary syndrome
- stage IV mycosis fungoides/Sezary syndrome
- recurrent mycosis fungoides/Sezary syndrome
- noncontiguous stage II small lymphocytic lymphoma
- noncontiguous stage II marginal zone lymphoma
- recurrent marginal zone lymphoma
- recurrent small lymphocytic lymphoma
- stage I marginal zone lymphoma
- stage I small lymphocytic lymphoma
- stage III small lymphocytic lymphoma
- stage III marginal zone lymphoma
- stage IV small lymphocytic lymphoma
- stage IV marginal zone lymphoma
- contiguous stage II marginal zone lymphoma
- contiguous stage II small lymphocytic lymphoma
- extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
- nodal marginal zone B-cell lymphoma
- splenic marginal zone lymphoma
- childhood myelodysplastic syndromes
- Lymphoma, Non-Hodgkin
- Neutropenia
- Lymphoma, Large-Cell, Immunoblastic
Name | Location |
|---|---|
| Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
